Aerobic exercise capacity is partly limited by vascular transport of oxygen and nutrients to end organs such as the heart and skeletal muscles. Vascular transport is, in turn, partly regulated by the elaboration of endothelial-derived nitric oxide (EDNO). Administration of physiologically acceptable compounds which enhance the elaboration of endogenous nitric oxide by the host allow for greater vascular transport and enhanced aerobic performance. Alternatively, compounds, or combinations of compounds, may be administered to enhance nitric oxide production, particularly in conjunction with the administration of a nitric oxide precursor to enhance aerobic performance.
Exercise capacity is limited by the rate by which oxygen can be taken up by a host (Schaible T F, Scheuer J: Cardiac adaptations to chronic exercise. Progress in Cardiovascular Disease 1985; 27:297-324; Wasserman K: Coupling of external to cellular respiration during exercise: the wisdom of the body revisited. American Journal of Physiology 1994; 266:E519-E539). In a generally healthy host, the rate of oxygen uptake, termed maximal velocity of oxygen uptake (VO.sub.2 max), is mostly limited by the oxygen transport capacity which is determined by the vascular conduction and distribution of blood flow (Barclay J K, Stainsby W N: The role of blood flow in limiting maximal metabolic rate in muscle. Medicine and Science in Sports and Exercise 1975; 7:116-119; di Prampero P E: An analysis of the factors limiting maximal oxygen consumption in healthy subjects. Chest 1992; 101:188S-191S). Therefore, the normal mechanisms which regulate blood flow during exercise can be limiting to aerobic exercise capacity. Furthermore, when these mechanisms are deranged, aerobic capacity may be further limited.
The production of nitric oxide by the endothelium (EDNO) contributes significantly to blood flow regulation and aerobic capacity during exercise (Maxwell A J, Schauble E, Bernstein D, Cooke J P: Limb blood flow during exercise is dependent upon nitric oxide. Circulation 1998;, Accepted for publication). This has been shown by the following series of experiments in the animal model. Administration of an inhibitor of the synthesis of EDNO acutely reduces aerobic capacity as measured by the VO.sub.2 max, the anaerobic threshold, running distance before exhaustion and aerobic work, as shown herein.
There are a significant number of cardiovascular disorders, where the individuals' ambulatory abilities are extensively impaired. These include individuals who suffer severe fatigue with exercise, which condition frequently is associated with heart failure. These disorders also include atherosclerosis affecting the coronary or limb arteries which can be manifested by angina (chest pain) or intermittent claudication (leg pain) with walking. Enhancing aerobic capacity to enhance performance would be of great advantage to these patients.
The use of L-arginine for prophylaxis and therapy in the case of atherosclerosis is taught in U.S. Pat. No. 5,5,428,070.